Preinvasive to Invasive: PD-1-Expressing Macrophages Shift Lung Cancer into High Gear.
Preinvasive to Invasive: PD-1-Expressing Macrophages Shift Lung Cancer into High Gear.
复制标题
侵袭前到侵袭：表达 PD-1 的巨噬细胞使肺癌进入高速运转状态。
DOI：
10.1158/0008-5472.can-22-1802
复制
发表时间：
2022
期刊：
影响因子：
11.2
通讯作者：
Lathia,JustinD
中科院分区：
文献类型：
--
作者：
Lee,Juyeun;Bayik,Defne;Lathia,JustinD
肺腺癌是肺癌最常见的亚型，在癌症中发病率第二高。免疫疗法已经彻底改变了肺癌治疗，但在肺腺癌患者中，检查点阻断应答率不到20%。由于肺腺癌由具有不同肿瘤侵袭表型和临床结局的异质性组织学亚群组成，因此了解基于组织学亚群的耐药机制至关重要。在本期中，Jang及其同事证明，表达PD-1的巨噬细胞是侵袭性肺腺癌的肿瘤免疫微环境（TiME）中的主要免疫细胞群，并负责推动肿瘤从侵袭前亚型进展为侵袭性亚型。表达PD-1的巨噬细胞具有促肿瘤发生性和高度可塑性，可能促进侵袭性实体瘤的发展。消融巨噬细胞重塑了TiME，并导致了有利的抗PD-1阻断反应，这表明在对单药治疗耐药的肺腺癌患者中可能存在联合治疗。目前的工作突出了肺腺癌进展期间TiME的时空动力学以及表达PD-1的巨噬细胞在驱动肿瘤发生以及对免疫疗法的抗性中的关键作用。第2593页
Lung adenocarcinoma is the most common subtype of lung cancer, which has the second highest incidence among cancers. Immunotherapy has revolutionized lung cancer treatment, yet the checkpoint blockade response rate is less than 20% in patients with lung adenocarcinoma. As lung adenocarcinoma consists of heterogeneous histologic subsets with diverse tumor invasion phenotypes and clinical outcomes, understanding the mechanisms of resistance based on the histology subset is essential. In the current issue, Jang and colleagues demonstrated that PD-1–expressing macrophages are the dominant immune cell population in the tumor-immune microenvironment (TiME) of invasive lung adenocarcinoma and are responsible for driving tumor progression from preinvasive to invasive subtypes. PD-1–expressing macrophages are protumorigenic and highly plastic, potentially promoting invasive solid tumor development. Ablation of macrophages remodels the TiME and leads to a favorable anti-PD-1 blockade response, suggesting a potential combination therapy in patients with lung adenocarcinoma resistant to monotherapy. This current work highlights the spatiotemporal dynamics of the TiME during lung adenocarcinoma progression and the critical role of PD-1–expressing macrophages in driving tumorigenesis as well as resistance to immunotherapy.See related article by Jang et al., p. 2593